P1224: EFFICACY OF RITUXIMAB AND BIOSIMILAR RITUXIMAB IN UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA, A DANISH POPULATION BASED ANALYSIS
Authors: A. Haujir, M. Tøstesen, T. C. El-Galaly, T. S. Larsen, J. Starklint, C. B. Poulsen, P. L. Josefsson, E. Clasen-Linde, A. Dessau-Arp, M. R. Clausen, J. M. Jørgensen
Journal: HemaSphere (2022)

Background: The standard treatment for diffuse large B-cell lymphoma (DLBCL) was for decades conventional chemotherapy eg. CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone). Around the year 2000 it became possible to add the monoclonal CD20 antibody rituximab, resulting in improved overall survival [1]. In 2017 biosimilars of rituximab were approved by the European Medicine Agency for the treatment of DLBCL, after showing non-inferiority to rituximab in randomized clinical trials[2–6]. Biosimilar rituximab is a cheaper alternative, and was implemented in danish hospitals for the treatment of non-Hodgkin lymphoma and DLBCL during 2018. Biosimilar rituximab has shown non-inferiority in randomized trials, but population-based analyses of the efficacy are still lacking. Aims: In this study we assessed the efficacy of biosimilar rituximab compared to rituximab on progression free survival (PFS) and overall survival (OS) in danish patients with previously untreated DLBCL. Methods: We used the population-based lymphoma registry in Denmark, LYFO, to identify adult patients with newly diagnosed DLBCL from January 2015 until January 2022. Patients treated with CHOP or CHOP-like treatment were included and we analyzed outcomes depending on type of rituximab. Primary CNS-lymphoma was excluded due to different treatment and prognosis. From pharmacies of the treating hospitals, we gathered information on the date of change to biosimilar rituximab. The primary endpoint was progression free survival defined as either registered relapse or death. We used Kaplan Meier curves and multivariable Cox regression analysis was used to evaluate outcomes. In the multivariable model we adjusted for the International Prognostic Index (IPI), sex and age as a continuous variable. Further we registered the type of chemotherapy in the first line of treatment and categorized these data as either CHOP/CHOEP or other. The proportional hazards assumption was evaluated graphically using log minus log plots. Results: We identified 2.372 patients with a median age of 70 years (range:18-95 years). There were 1.049 in the rituximab group with a median age of 69 years and 1.343 in the biosimilar rituximab group, median age 71 years. The International Prognostic Index distribution was comparable between groups. The fraction of DLBCL patients receiving CHOP/CHOEP based regimen was lower in the biosimilar rituximab group, 94% vs. 98% respectively (Table 1). The 3-year PFS was 71.8% (95% confidence interval[CI] 69.1-74.3) and 72.2% (95% CI 69.3-74.9) for rituximab and biosimilar rituximab treated patients (Figure 1). In the multivariable analyses we found no difference in PFS or OS with a hazard ratio of 0.94 (95% CI 0.81 - 1.10) and 0.99 (95% CI 0.83 - 1.17). TABLE 1 - TABLE 1 Rituximab N = 1.049 Biosimilar rituximab N = 1.343 Total Male 622 (59.3) 762 (57.6) 1.384 Female 427 (40.7) 561 (42.4) 988 Age, yrs, median (range) 69 (18-93) 71 (18-95) 70 International Prognostic Index Low 297 (28.3) 342 (25.9) 639 Low intermediate 233 (22.2) 320 (24.2) 553 High intermediate 279 (26.6) 362 (27.4) 641 High 212 (20.2) 277 (20.9) 489 missing 28 (82.7) 22 (1.7) 50 R-CHOP/CHOEP‡ 1.026 (98) 1.245 (94) Total 1.137 1.235 2.372 Image:Summary/Conclusion: In this population-based study we found no significant difference in PFS or OS in patients treated with chemotherapy in combination with rituximab or biosimilar rituximab. Fewer patients were treated with CHOP/CHOEP in the biosimilar group due to an increased use of mini-CHOP and more intensive regimens. These results substantiate the continued use of biosimilar rituximab in patients with DLBCL.